Total Body Irradiation and Lung Function and Structure. Hemapoietic malignancies, such as acute leukemia, are often treated with bone marrow transplantation (BMT) which is preceded by total body irradiation (TBI). A major reason for failure of this procedure is death, due to interstitial pneumonitis. The lung is considered the critical organ following TBI. Unfortunately, there is no consensus as to what total dose and dose rate of TBI should be used in the clinic. It would be important to know what relationship exists between total radiation dose, dose rate and lung function and structure following. Also, more needs to be known about how much impairment of lung function and alteration at lung structure would occur if a given total dose of TBI were split into 2 equal fractions separated by various intervals of time. We propose to investigate these relationships using 2 inbred murine models. For experiments related to the effects of dose rate and total dose unanesthetized mice will receive various total does of 60Co irradiation at either 2.5, 5, 26 or 45 rad/min (dose rates used in the clinic). For each dose rate the total doses given will range between a maximum dose that could be tolerated without notable alterations in lung function and a dose which would produce severe change in lung function. Intermediate doses will be separated by increments of 150 or 200 rad. Animals will be given BMT 16-24 hours after completion of irradiation. Lung function and histology will be investigated at definite intervals following irradiation. For experiments related to dose fractionation 1400 rad TBI will be given (at 26 rad/min) as either a single dose or as 2 equal fractions separated by various intervals of time. BMT will be given after the second dose of TBI. Lung function and structure will be investigated at 16 weeks post-irradiation. The functions that will be studied include: steady state diffusion capacity of carbon monoxide, static lung compliance, ventilation rate and amplitude, minimum lung volume, and possibly perfusion rate. Histological parameters include: extent of lung involvement, thickness of alveolar septae, extent of collagen deposition and extent of vascular injury.